Graft-versus-tumor effect: Difference between revisions

Latest revision as of 19:18, 22 March 2025

Immune response against tumor cells by transplanted immune cells

Graft-versus-tumor effect[edit]

The graft-versus-tumor effect (GVT) is a beneficial immunological phenomenon that occurs following allogeneic hematopoietic stem cell transplantation (HSCT). It involves the recognition and destruction of tumor cells by the donor's immune cells, which are part of the graft. This effect is a critical component of the therapeutic success of allogeneic HSCT in treating certain types of cancer, particularly hematological malignancies.

Mechanism[edit]

The GVT effect is primarily mediated by donor T cells and natural killer cells that are transferred to the recipient during the transplantation process. These immune cells recognize and attack residual tumor cells in the recipient's body. The process involves several steps:

Antigen Recognition: Donor T cells recognize tumor-associated antigens presented by the recipient's antigen-presenting cells.
Activation and Proliferation: Upon recognition, donor T cells become activated and proliferate.
Cytotoxic Response: Activated T cells and natural killer cells exert cytotoxic effects on tumor cells through the release of cytokines and direct cell-to-cell contact.

Clinical Significance[edit]

The GVT effect is a double-edged sword. While it can lead to the eradication of tumor cells, it is closely related to the graft-versus-host disease (GVHD), a condition where donor immune cells attack the recipient's healthy tissues. Balancing the GVT effect and minimizing GVHD is a major challenge in allogeneic HSCT.

Applications[edit]

The GVT effect is particularly effective in treating:

Strategies to Enhance GVT[edit]

Several strategies are being explored to enhance the GVT effect while minimizing GVHD:

Donor Lymphocyte Infusion (DLI): Infusing additional donor lymphocytes after transplantation to boost the GVT effect.
Cytokine Therapy: Using cytokines such as interleukin-2 to stimulate donor immune cells.
Genetic Engineering: Modifying donor T cells to enhance their tumor-targeting capabilities.

Related pages[edit]

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-{{context|date=October 2013}}
+{{Short description|Immune response against tumor cells by transplanted immune cells}}
-'''Graft-versus-tumor effect''' (GvT) appears after [[allotransplantation|allogeneic]] [[hematopoietic stem cell transplantation]] (HSCT). The graft contains donor [[T cell]]s (T lymphocytes) that can be beneficial for the recipient by eliminating residual [[malignancy|malignant]] cells.<ref name="pmid23482243">{{cite journal|vauthors=Thompson LF, Tsukamoto H, Chernogorova P, Zeiser R | title=A delicate balance: CD73-generated adenosine limits the severity of graft vs. host disease but also constrains the allogeneic graft vs. tumor effect | journal=Oncoimmunology | year= 2013 | volume= 2 | issue= 1 | pages= e22107 | pmid=23482243 | doi=10.4161/onci.22107 | pmc=3583907 }}</ref> GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune control of hematologic malignancies.<ref name="pmid19029455">{{cite journal| author=Kolb HJ| title=Graft-versus-leukemia effects of transplantation and donor lymphocytes | journal=Blood | year= 2008 | volume= 112 | issue= 12 | pages= 4371–83 | doi=10.1182/blood-2008-03-077974 | pmc= | pmid=19029455  }}</ref> This effect applies in [[myeloma]] and lymphoid [[leukemia]]s, [[lymphoma]], [[multiple myeloma]] and possibly [[breast cancer]].<ref name="pmid10561256">{{cite journal|vauthors=Childs RW, Clave E, Tisdale J, Plante M, Hensel N, Barrett J | title=Successful treatment of metastatic renal cell carcinoma with a nonmyeloablative allogeneic peripheral-blood progenitor-cell transplant: evidence for a graft-versus-tumor effect | journal=J Clin Oncol | year= 1999 | volume= 17 | issue= 7 | pages= 2044–9 | doi= 10.1200/jco.1999.17.7.2044| pmc= | pmid=10561256  }}</ref> It is closely linked with [[graft-versus-host disease]] (GvHD), as the underlying principle of [[alloimmunity]] is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect.<ref name="pmid1292584">{{cite journal|vauthors=Vagianos C, Polydorou A, Karatzas T, Vagenas C, Stavropoulos M, Androulakis J | title=Successful treatment of postoperative external biliary fistula by selective nasobiliary drainage | journal=HPB Surg | year= 1992 | volume= 6 | issue= 2 | pages= 115–20; discussion 120–4 | pmid=1292584 | doi= 10.1155/1992/58436| pmc=2443016 }}</ref>
+== Graft-versus-tumor effect ==
-The biology of GvT response still isn’t fully understood but it is probable that the reaction with polymorphic minor [[histocompatibility]] antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved.<ref name="pmid15774790">{{cite journal |vauthors=Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R, etal | title=Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning | journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 9 | pages= 1993–2003 | doi=10.1200/JCO.2005.08.136 | pmc= | pmid=15774790  | url=http://orbi.ulg.ac.be/handle/2268/102049 }}</ref><ref name="pmid18242060">{{cite journal|vauthors=Rezvani AR, Storb RF | title=Separation of graft-vs.-tumor effects from graft-vs.-host disease in allogeneic hematopoietic cell transplantation | journal=J Autoimmun | year= 2008 | volume= 30 | issue= 3 | pages= 172–9 | pmid=18242060 | doi=10.1016/j.jaut.2007.12.002 | pmc=2329571 }}</ref> This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers (NK cells) as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.<ref name="pmid18242060" />
+The '''graft-versus-tumor effect''' (GVT) is a beneficial immunological phenomenon that occurs following [[allogeneic hematopoietic stem cell transplantation]] (HSCT). It involves the recognition and destruction of [[tumor]] cells by the donor's immune cells, which are part of the graft. This effect is a critical component of the therapeutic success of allogeneic HSCT in treating certain types of [[cancer]], particularly [[hematological malignancies]].
-==See also==
+== Mechanism ==
+The GVT effect is primarily mediated by [[donor T cells]] and [[natural killer cells]] that are transferred to the recipient during the transplantation process. These immune cells recognize and attack residual tumor cells in the recipient's body. The process involves several steps:
+# '''Antigen Recognition''': Donor T cells recognize tumor-associated antigens presented by the recipient's [[antigen-presenting cells]].
+# '''Activation and Proliferation''': Upon recognition, donor T cells become activated and proliferate.
+# '''Cytotoxic Response''': Activated T cells and natural killer cells exert cytotoxic effects on tumor cells through the release of [[cytokines]] and direct cell-to-cell contact.
+== Clinical Significance ==
+The GVT effect is a double-edged sword. While it can lead to the eradication of tumor cells, it is closely related to the [[graft-versus-host disease]] (GVHD), a condition where donor immune cells attack the recipient's healthy tissues. Balancing the GVT effect and minimizing GVHD is a major challenge in allogeneic HSCT.
+== Applications ==
+The GVT effect is particularly effective in treating:
+* [[Acute myeloid leukemia]] (AML)
+* [[Chronic myeloid leukemia]] (CML)
+* [[Non-Hodgkin lymphoma]]
+* [[Multiple myeloma]]
+== Strategies to Enhance GVT ==
+Several strategies are being explored to enhance the GVT effect while minimizing GVHD:
+* '''Donor Lymphocyte Infusion (DLI)''': Infusing additional donor lymphocytes after transplantation to boost the GVT effect.
+* '''Cytokine Therapy''': Using cytokines such as [[interleukin-2]] to stimulate donor immune cells.
+* '''Genetic Engineering''': Modifying donor T cells to enhance their tumor-targeting capabilities.
+== Related pages ==
 * [[Graft-versus-host disease]]
 * [[Hematopoietic stem cell transplantation]]
+* [[Immunotherapy]]
+* [[Cancer treatment]]
-==References==
-{{Reflist}}
-[[Category:Transplantation medicine]]
 [[Category:Immunology]]
+[[Category:Oncology]]
+[[Category:Hematology]]
-{{oncology-stub}}
-{{dictionary-stub1}}
-{{No image}}